The shortcomings of the "pill" and the various intrauterine devices have lent impetus to the continuing search for safe, simple and effective means of contraception. Medicinal induction of very early abortion or resorption of embryos offers a practical way of dealing with unwanted pregnancies, because an interceptive drug would only require use after a missed menses. Early work on the prostaglandins suggested that this type of compounds might serve as a practical early abortifacient. Subsequent studies revealed their side effects, which are severe enough to make it unlikely that these drugs could be used in the home on a prescription basis. Furthermore, the mechanism of action of natural prostaglandins, or 9-oxa- or-thiaprostaglandins, appears to differ between various animal species, including rodents and subhuman primates, as compared with human beings. In the former, they may disrupt the function of the corpus luteum, while in the latter their action appears to be mainly oxytocic.
Another type of drug, aminoglutethimide, has aroused interest because it blocks the conversion of cholesterol to pregnenolone in the steroid pathway. It inhibits progesterone secretion in pregnant and non-pregnant animals and human beings and can be used, according to U.S. Pat. No. 3,836,659, for reducing the number of fetuses in pregnant females. Unfortunately, .alpha.-(4-aminophenyl)-.alpha.-lower alkylglutarimides have a low potency and short duration of action for inducing abortion in rats. They must be given in high doses, which cause marked side effects, i.e. their originally discovered anticonvulsant effects, including central nervous system depression.
Surprisingly it was found that the natural prostaglandins and analogs thereof, e.g. those disclosed in U.S. Pat. Nos. 3,657,328, 3,678,092 or J. Pharm. Sci. 61, 1861 (1972), as well as 9-oxa- and 9-thiaprostaglandins, e.g. those disclosed in U.S. Pat. Nos. 3,883,659 and 3,970,670, despite the extremely short duration of action of the natural products, and in doses which individually did not interfere with pregnancy, synergistically enhance the interceptive action of said glutarimides, also given in doses markedly below those taught in U.S. Pat. No. 3,836,659, resulting in the resorption of all or most fetuses.